Phospholipids play critical roles in hormone sensitive adenylate cyclase systems. We have characterized a solubilized preparation of cardiac adenylate cyclase which is unresponsive to hormone stimulation. Phosphatidylserine restores the responsiveness of cardiac adenlyate cyclase to glucagon and monophosphatidylinositol restores its responsiveness to catecholamines. We have recently demonstrated that glucagon stimulates the incorporation of P32 and C14-serine into phosphatidylserine in heart muscle slices. The increase above control was about sixfold at 30 minutes for P32 and twelvefold as early as three minutes for C14-serine. A smaller but significant incorporation of P32 into phosphatidylethanolamine was also observed. No significant incorporation of C14-serine into any other phospholipid was found. Dibutyryl cyclic 3', 5'-AMP did not increase the incorporation of P32 or C14-serine into phosphatidylserine. We have also described the formation of a small molecular weight peptide (MW approx. 1000) inhibitor of adenylate cyclase produced by the in situ perfused rat liver under hypocalcemic conditions. The inhibitor non-competitively blocks epinephrine activation of cardiac adenylate cyclase and epinephrine, glucagon, and parathyroid hormone activation of renal cortical and hepatic adenylate cyclase. The inhibitor which is also found in rat heart is not species specific and exerts its effects in cat and dog adenylate cyclases equally well. The inhibitor is heat-stable, acid-stable, alkali-labile and is destroyed by trypsin, leucine aminopeptidase and elastase. It is unclear whether the peptide is synthesized by the liver and heart or whether it is a breakdown product of a larger molecular weight protein. The factor has been purified approximately 50,000-fold. BIBLIOGRAPHIC REFERENCES: Levey, G. S., Weiss, S. R. and E. Ruiz: Characterization of the glucagon receptor in a pheochromocytoma. J. Clin. Endo. Metab. 40:720-723, 1975. Levey, G. S.: The Glucagon receptor and adenylate cyclase. Earl W. Sutherland Memorial Symposium, Metabolism, 24:301-310, 1975.